Researchers from Yale University and affiliated organizations published data from a study that aimed to assess the mechanistic and pathophysiological importance of plaque-associated axonal spheroids (PAASs) in Alzheimer’s disease (AD).

In 2021, Biogen Inc.’s Aduhelm (aducanumab) became the first amyloid-targeting therapy to win U.S. FDA approval in Alzheimer’s disease. After decades and dozens of failed phase III trials, the drug was granted accelerated approval in June 2021. In January 2022, however, the U.S. Center for Medicare & Medicaid Services said it would only cover use of Alzheimer’s MAbs targeting amyloid in NIH trials or trials it approved, thus appearing to call into question the rigor of FDA-approved trials.

2021 was the year Aduhelm (aducanumab, Biogen Inc.) was approved as the first amyloid-β-busting drug for Alzheimer’s disease. And in 2022, there was as much need for an effective AD drug as ever. Aduhelm’s commercial fate was sealed with the decision of the Center for Medicare & Medicaid Services (CMS) that the drug would only be reimbursed in clinical trials approved by the CMS or the NIH.

Alzheimer’s disease has a higher incidence in women. This sex difference was associated with a modification of certain proteins of the immune system. According to a recent study, the drop in estrogen with menopause increased the expression in the brain of a neurotransmitter, nitric oxide (NO), generating the S-nitrosylation of complement factor C3 (abbreviated SNO-C3), which activated the microglia.

Researchers have identified a link between amyloid plaques and dysfunctional neuronal conduction in animal models of Alzheimer’s disease (AD). Their study, which was published in the Dec. 1, 2022, issue of Nature, suggests new ways to think about AD, as well as badly needed potential alternatives to plaque removal to fight the disease.